Intratumoral administration of mRNA-1273 vaccine delays melanoma growth in mice

BackgroundImmunotherapies are advantageous for treating cancers; however, their efficacy is limited in unresponsive hosts with "cold" tumor microenvironments. This limitation primarily stems from the lack of infiltrating CD8+ T cells, which are major effectors of the anti-cancer immune response. Here, we demonstrate the effects of intratumoral (IT) injections of the COVID-19 mRNA vaccine on the impairment of tumor growth in mice. MethodsEstablished B16F10 subcutaneous tumor models in wild type mice were used to evaluate the tumor response from IT administration of mRNA-1273. We compared treatment outcomes, immune composition, and transcriptomic effects from mRNA-1273 using survival studies, intravital imaging, flow cytometry, single-cell RNA sequencing, and abscopal studies. The ability of mRNA-1273 to enhance immune checkpoint therapy response was also evaluated. ResultsTumor growth and survival studies following a single IT injection of the COVID-19 mRNA-1273 vaccine showed significant tumor suppression and prolonged survival in tumor-bearing mice. mRNA-1273 treatment resulted in a significant increase in CD8+ T cell infiltration into the tumor microenvironment, as observed using intravital imaging and flow cytometry. Further tumor growth suppression was achieved using additional mRNA-1273 treatments. Combination administration of mRNA-1273 with immune checkpoint therapies demonstrated enhanced effects, further delaying tumor growth and improving the survival time of tumor-bearing mice. ConclusionIT injection of mRNA-1273 significantly reduced tumor growth and enhanced CD8+ T cells in the tumor microenvironment. Tumor suppression was further enhanced following multiple injections of mRNA-1273 or when combined with immune checkpoint therapies. This study demonstrates that mRNA vaccines may be used as adjuvants for immunotherapies. What is already known on this topicO_LIMost cancer patients develop adequate antibody response to vaccination with mRNA-1273 and produce spike-specific T cell responses. However, it is unclear if the mRNA-1273 vaccine can be used to elicit anti-tumor T cell responses. C_LI What this study addsO_LIIntratumoral injection of mRNA-1273 significantly delayed melanoma growth. C_LIO_LITreatment with mRNA-1273 significantly increased CD8+ T cell infiltration into the tumor microenvironment. C_LIO_LIEnhanced effects of combination mRNA-1273 and immune checkpoint therapy in anti-tumor immunity. C_LI How this study might affect research, practice, or policyO_LImRNA vaccine may be an effective adjuvant with immune checkpoint therapy. C_LI